Search

Aims: Cerebral complications after cardiac arrest (CA) remain a major problem worldwide. The aim was to test the effects of sodium-ß-hydroxybutyrate (SBHB) infusion on brain injury in a clinically relevant swine model of CA., Results: CA was electrically induced in 20 adult swine. After 10 min, cardiopulmonary resuscitation was performed for 5 min. After return of spontaneous circulation (ROSC), the animals were randomly assigned to receive an infusion of balanced crystalloid (controls, n = 11) or SBHB (theoretical osmolarity 1189 mOsm/l, n = 8) for 12 h. Multimodal neurological and cardiovascular monitoring were implemented in all animals. Nineteen of the 20 animals achieved ROSC. Blood sodium concentrations, osmolarity and circulating KBs were higher in the treated animals than in the controls. SBHB infusion was associated with significantly lower plasma biomarkers of brain injury at 6 (glial fibrillary acid protein, GFAP and neuron specific enolase, NSE) and 12 h (neurofilament light chain, NFL, GFAP and NSE) compared to controls. The amplitude of the stereoelectroencephalograph (sEEG) increased in treated animals after ROSC compared to controls. Cerebral glucose uptake was lower in treated animals., Conclusions: In this experimental model, SBHB infusion after resuscitated CA was associated with reduced circulating markers of cerebral injury and increased sEEG amplitude., (© 2024. The Author(s).)

Background: The aim of this study was to assess the prevalence of delayed deterioration of electroencephalogram (EEG) in patients with cardiac arrest (CA) without early highly malignant patterns and to determine their associations with clinical findings., Methods: This was a retrospective study of adult patients with CA admitted to the intensive care unit (ICU) of a university hospital. We included all patients with CA who had a normal voltage EEG, no more than 10% discontinuity, and absence of sporadic epileptic discharges, periodic discharges, or electrographic seizures. Delayed deterioration was classified as the following: (1) epileptic deterioration, defined as the appearance, at least 24 h after CA, of sporadic epileptic discharges, periodic discharges, and status epilepticus; or (2) background deterioration, defined as increasing discontinuity or progressive attenuation of the background at least 24 h after CA. The end points were the incidence of EEG deteriorations and their association with clinical features and ICU mortality., Results: We enrolled 188 patients in the analysis. The ICU mortality was 46%. Overall, 30 (16%) patients presented with epileptic deterioration and 9 (5%) patients presented with background deterioration; of those, two patients presented both deteriorations. Patients with epileptic deterioration more frequently had an out-of-hospital CA, and higher time to return of spontaneous circulation and less frequently had bystander resuscitation than others. Patients with background deterioration showed a predominantly noncardiac cause, more frequently developed shock, and had multiple organ failure compared with others. Patients with epileptic deterioration presented with a higher ICU mortality (77% vs. 41%; p < 0.01) than others, whereas all patients with background deterioration died in the ICU., Conclusions: Delayed EEG deterioration was associated with high mortality rate. Epileptic deterioration was associated with worse characteristics of CA, whereas background deterioration was associated with shock and multiple organ failure., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose: To review the prevalence and describe the characteristics, of cases with late-onset intracorneal ring segments (ICRS) keratopathy in a multicenter study., Methods: A retrospective multicentric case-series study was performed in a specialized keratoconus service, from Buenos Aires, Argentina. An electronic clinical chart from patients with ICRS keratopathy between January 1999 and January 2019 was reviewed. We included cases with late-onset distal-apical ICRS keratopathy, which was defined as a persistent corneal lesion developed 12 months or later after implantation, located over, around, or closer to the ICRS. All the surgeries were performed by a manual corneal tunnel creation technique. Samples were taken to rule out infectious etiology., Results: From 5217 eyes that underwent ICRS implantation, 13 cases (0.24%) were detected. The keratopathy onset was 72 ± 42.98 months (29-133) after ICRS implantation. Cultures were negative in all cases. An ICRS exchange was made for five cases in stage I and four in stage II. Four cases presented with partial ICRS extrusion in stage III. ICRS exchange was possible in two of them and a penetration keratoplasty was necessary for the rest. All cases remained stable 1 year after surgical procedures., Conclusions: A late-onset distal-apical ICRS keratopathy was detected with low prevalence (0.24%) in a large sample. It was classified into three stages according to its severity. Different treatments were selected for each stage, obtaining stable results 1 year after treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Sepsis-associated encephalopathy (SAE) is frequent in septic patients. Electroencephalography (EEG) is very sensitive to detect early epileptic abnormalities, such as seizures and periodic discharges (PDs), and to quantify their duration (the so-called burden). However, the prevalence of these EEG abnormalities in septic patients, as well as their effect on morbidity and mortality, are still unclear. The aims of this study were to assess whether the presence of electrographic abnormalities (i.e. the absence of reactivity, the presence and burden of seizures and PDs) was associated with functional outcome and mortality in septic patients and whether these abnormalities were associated with sepsis-associated encephalopathy (SAE)., Methods: We prospectively included septic patients, without known chronic or acute intracranial disease or pre-existing acute encephalopathy, requiring ICU admission in a tertiary academic centre. Continuous EEG monitoring was started within 72 h after inclusion and performed for up to 7 days. A comprehensive assessment of consciousness and delirium was performed twice daily by a trained neuropsychologist. Primary endpoints were unfavourable functional outcome (UO, defined as a Glasgow Outcome Scale-Extended-GOSE-score < 5), and mortality collected at hospital discharge and secondary endpoint was the association of PDs with SAE. Mann-Whitney, Fisher's exact and χ 2 tests were used to assess differences in variables between groups, as appropriate. Multivariable logistic regression analysis with in-hospital mortality, functional outcome, SAE or PDs as the dependent variables were performed., Results: We included 92 patients. No seizures were identified. Nearly 25% of patients had PDs. The presence of PDs and PDs burden was associated with UO in univariate (n = 15 [41%], p = 0.005 and p = 0.008, respectively) and, for PDs presence, also in multivariate analysis after correcting for disease severity (OR 3.82, IC 95% [1.27-11.49], p = 0.02). The PDs burden negatively correlated with GOSE (Spearman's coefficient ρ = - 0.2, p = 0.047). The presence of PDs was also independently associated with SAE (OR 8.98 [1.11-72.8], p = 0.04). Reactivity was observed in the majority of patients and was associated with outcomes (p = 0.044 for both functional outcome and mortality)., Conclusion: Our findings suggest that PDs and PDs burden are associated with SAE and might affect outcome in septic patients., (© 2023. The Author(s).)

Purpose: Evaluate the clinical outcomes of the secondary piggyback add-on IOL implantation in the ciliary sulcus for pseudophakic patients previously implanted with a monofocal IOL, who pursue a spectacle-free option after IOL surgery., Methods: A prospective case series including seven pseudophakic patients who underwent an in-the-bag monofocal IOL implantation. All eyes underwent a piggyback IOL implantation of the new sulcus designed A4 AddOn IOL in the ciliary sulcus as a secondary procedure for pseudophakic patients pursuing a spectacle-free option for near and intermediate distance after IOL surgery., Results: Seven eyes from six patients were included in this study, from which 4 (71.43%) were female, with a mean age of 58.33 ± 3.5 years (range 54-63; 95% CI 54.66, 62.01). The postoperative spherical equivalent at the 3-month visit was -0.10 m ± 0.82. Also, the UDVA was 0.11 ± 0.08 logMAR, the UIVA 0.01 ± 0.03, and the UNVA 0.01 ± 0.03 3 months after their surgical procedure., Conclusions: The A4 AddOn multifocal IOL's secondary piggyback implant is an efficient alternative for monofocal pseudophakic patients seeking presbyopia solutions. This sulcus-designed IOL provides an optimal visual outcome for near and distance vision.

Introduction: Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA., Methods: After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C., Results: Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls., Conclusions: In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury., (© 2023. The Author(s).)

Sepsis associated encephalopathy (SAE) is a frequent complication of sepsis and is associated with a higher risk of short-term mortality and long-term cognitive impairment. The EEG is a sensitive complement of the clinical examination that can also detect and quantify encephalopathy and identify features with prognostic value, such as lack of reactivity. Moreover, despite their effect on outcome is still debated, the EEG is the only tool to detect non-convulsive seizures which can occur in a septic setting. Understanding the pathophysiology of SAE is fundamental to define potential therapeutic targets. Neuroinflammation plays an important role in the development of SAE and many blood and imaging biomarkers have recently shown a promising ability to distinguish SAE form non-SAE patient. In recent years, some interesting mediators of inflammation were successfully targeted in animal models, with a significant reduction in the neuroinflammation and in sepsis-induced cognitive decline. However, the complexity of the host response to sepsis currently limits the use of immunomodulation therapies in humans. Alteration in regulatory systems of cerebral blood flow, namely cerebral autoregulation (CA) and neurovascular coupling, contribute to SAE development. Nowadays, clinicians have access to different tools to assess them at the bedside and CA-based blood pressure protocols should be implemented to optimize cerebral perfusion. Its inauspicious consequences, its complex physiopathology and the lack of efficacious treatment make of SAE a highly active research subject.

Non-convulsive seizures and status epilepticus are frequent and associated with increased mortality in septic patients. However, the mechanism through which seizures impact outcome in these patients is unclear. As previous studies yielded an alteration of neurovascular coupling (NVC) during sepsis, we hypothesized that non-convulsive seizures, might further impair NVC, leading to brain tissue hypoxia. We used a previously developed ovine model of sepsis. Animals were allocated to sham procedure or sepsis; septic animals were studied either during the hyperdynamic phase (sepsis group) or after septic shock occurrence (septic shock group). After allocation, seizures were induced by cortical application of penicillin. We recorded a greater seizure-induced increase in the EEG gamma power in the sepsis group than in sham. Using a neural mass model, we also found that the theoretical activity of the modeled inhibitory interneurons, thought to be important to reproduce gamma oscillations, were relatively greater in the sepsis group. However, the NVC was impaired in sepsis animals, despite a normal brain tissue oxygenation. In septic shock animals, it was not possible to induce seizures. Cortical activity declined in case of septic shock, but it did not differ between sham or sepsis animals. As the alteration in NVC preceded cortical activity reduction, we suggest that, during sepsis progression, the NVC inefficiency could be partially responsible for the alteration of brain function, which might prevent seizure occurrence during septic shock. Moreover, we showed that cardiac output decreased during seizures in sepsis animals instead of increasing as in shams. The alteration of the seizure-induced systemic hemodynamic variations in sepsis might further affect cerebrovascular response to neuronal activation. Our findings support the hypothesis that anomalies in the cerebral blood flow regulation may contribute to the sepsis-associated encephalopathy and that seizures might be dangerous in such a vulnerable setting., (© 2022. The Author(s).)

Background: Electroencephalography (EEG) is widely used to monitor critically ill patients. However, EEG interpretation requires the presence of an experienced neurophysiologist and is time-consuming. Aim of this study was to evaluate whether parameters derived from an automated pupillometer (AP) might help to assess the degree of cerebral dysfunction in critically ill patients., Methods: Prospective study conducted in the Department of Intensive Care of Erasme University Hospital in Brussels, Belgium. Pupillary assessments were performed using the AP in three subgroups of patients, concomitantly monitored with continuous EEG: "anoxic brain injury", "Non-anoxic brain injury" and "other diseases". An independent neurologist blinded to patient's history and AP results scored the degree of encephalopathy and reactivity on EEG using a standardized scale. The mean value of Neurologic Pupil Index (NPi), pupillary size, constriction rate, constriction and dilation velocity (CV and DV) and latency for both eyes, obtained using the NPi®-200 (Neuroptics, Laguna Hills, CA, USA), were reported., Results: We included 214 patients (mean age 60 years, 55% male). EEG tracings were categorized as: mild ( n = 111, 52%), moderate ( n = 65, 30%) or severe ( n = 16, 8%) encephalopathy; burst-suppression ( n = 19, 9%) or suppression background ( n = 3, 1%); a total of 38 (18%) EEG were classified as "unreactive". We found a significant difference in all pupillometry variables among different EEG categories. Moreover, an unreactive EEG was associated with lower NPi, pupil size, pupillary reactivity, CV and DV and a higher latency than reactive recordings. Low DV (Odds ratio 0.020 [95% confidence intervals 0.002-0.163]; p < 0.01) was independently associated with an unreactive EEG, together with the use of analgesic/sedative drugs and high lactate concentrations. In particular, DV values had an area under the curve (AUC) of 0.86 [0.79-0.92; p < 0.01] to predict the presence of unreactive EEG. In subgroups analyses, AUC of DV to predict unreactive EEG was lower (0.72 [0.56-0.87]; p < 0.01) in anoxic brain injury than Non-anoxic brain injury (0.92 [0.85-1.00]; p < 0.01) and other diseases (0.96 [0.90-1.00]; p < 0.01)., Conclusions: This study suggests that low DV measured by the AP might effectively identify an unreactive EEG background, in particular in critically ill patients without anoxic brain injury., Competing Interests: FT and MO are scientific advisors for NeurOptics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peluso, Ferlini, Talamonti, Ndieugnou Djangang, Gouvea Bogossian, Menozzi, Annoni, Macchini, Legros, Severgnini, Creteur, Oddo, Vincent, Gaspard and Taccone.)

Background: Anoxic brain injuries represent the main determinant of poor outcome after cardiac arrest (CA). Large animal models have been described to investigate new treatments during CA and post-resuscitation phase, but a detailed model that includes extensive neuromonitoring is lacking., Method: Before an electrically-induced 10-minute CA and resuscitation, 46 adult pigs underwent neurosurgery for placement of a multifunctional probe (intracranial pressure or ICP, tissue oxygen tension or PbtO 2 and cerebral temperature) and a bolt-based technique for the placement and securing of a regional blood flow probe and two sEEG electrodes; two modified cerebral microdialysis (CMD) probes were also inserted in the frontal lobes and accidental misplacement was prevented using a perforated head support., Result: 42 animals underwent the CA procedure and 41 achieved the return of spontaneous circulation (ROSC). In 4 cases (8.6%) an adverse event took place during preparation, but only in two cases (4.3%) this was related to the neurosurgery. In 6 animals (13.3%) the minor complications that occurred resolved after probe repositioning., Conclusion: Herein we provide a detailed comprehensive neuromonitoring approach in a large animal model of CA that might help future research., (© 2022 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Introduction: Hyperammonemia (HA) is a potential side-effect of valproate (VPA) treatment, which has been described during long-term administration. The aim of this study was to evaluate the incidence, the impact and the risk factors of HA in critically ill patients., Methods: We reviewed the data of all adult patients treated in our mixed 35-bed Department of Intensive Care over a 12-year period (2004-2015) who: a) were treated with VPA for more than 72 h and b) had at least one measurement of ammonium and VPA levels during the ICU stay; patients with Child-Pugh C liver cirrhosis were excluded. HA was defined as ammonium levels above 60 μg/dl., Results: Of a total of 2640 patients treated with VPA, 319 patients met the inclusion criteria (median age 64 years; male gender 55%); 78% of them were admitted for neurological reasons and ICU mortality was 30%. Median ammonium levels were 88 [63-118] µg/dl. HA was found in 245 (77%) patients. For those patients with HA, median time from start of VPA therapy to HA was 3 [2-5] days. In a multivariable analysis, high VPA serum levels, mechanical ventilation and sepsis were independently associated with HA during VPA therapy. In 98/243 (40%) of HA patients, VPA was interrupted; VPA interruption was more frequent in patients with ammonium levels > 100 μg/dl than others (p = 0.001). HA was not an independent predictor of ICU mortality or poor neurological outcome., Conclusions: In this study, HA was a common finding during treatment with VPA in acutely ill patients. VPA levels, sepsis and mechanical ventilation were risk factors for HA. Hyperammonemia did not influence patients' outcome., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The increase in neuronal activity induced by a single seizure is supported by a rise in the cerebral blood flow and tissue oxygenation, a mechanism called neurovascular coupling (NVC). Whether cerebral and systemic hemodynamics are able to match neuronal activity during recurring seizures is unclear, as data from rodent models are at odds with human studies. In order to clarify this issue, we used an invasive brain and systemic monitoring to study the effects of chemically induced non-convulsive seizures in sheep. Despite an increase in neuronal activity as seizures repeat (Spearman's ρ coefficient 0.31, P < 0.001), ictal variations of cerebral blood flow remained stable while it progressively increased in the inter-ictal intervals (ρ = 0.06, P = 0.44 and ρ = 0.22; P = 0.008). We also observed a progressive reduction in the inter-ictal brain tissue oxygenation (ρ =  - 0.18; P = 0.04), suggesting that NVC was unable to compensate for the metabolic demand of these closely repeating seizures. At the systemic level, there was a progressive reduction in blood pressure and a progressive rise in cardiac output (ρ =  - 0.22; P = 0.01 and ρ = 0.22; P = 0.01, respectively), suggesting seizure-induced autonomic dysfunction., (© 2021. The Author(s).)

Brain metastasis (BM) is a frequent complication of systemic cancer usually associated with poor prognosis. Survival depends on numerous factors, which complicates prognosis and treatment. It has been suggested that BM growing from previously dormant disseminated tumour cells (DTCs) may exhibit a milder phenotype than BM derived from continuously progressing metastatic cells; however, to the best of our knowledge, the prognosis of patients presenting with BM from dormant DTCs is unknown. The present study retrospectively compared survival data, collected from a single neurosurgical centre, between patients presenting with BM from previously dormant DTCs and patients with non-dormant BM. A total of 262 medical records were reviewed. In the univariate Cox regression analysis, the median survival of the dormant BM group was statistically longer than that of the non-dormant group (P=0.048); a trend towards a longer survival persisted after correcting for age, presence of breast cancer and treatment options (P=0.057), which are all factors known to influence outcome. The improved outcome of these patients could be considered in models for prognostication. Moreover, the development of therapies able to eradicate dormant DTCs could provide a new promising strategy to prolong the survival of patients with a favourable prognosis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ferlini et al.)

Objective: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes., Methods: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes., Results: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49])., Interpretation: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883., (© 2021 American Neurological Association.)

Background: Electroencephalography (EEG) is widely used in the monitoring of critically ill comatose patients, but its interpretation is not straightforward. The aim of this study was to evaluate whether there is a correlation between EEG background pattern/reactivity to stimuli and automated pupillometry in critically ill patients., Methods: Prospective assessment of pupillary changes to light stimulation was obtained using an automated pupillometry (NeuroLight Algiscan, ID-MED, Marseille, France) in 60 adult patients monitored with continuous EEG. The degree of encephalopathy and EEG reactivity were scored by 3 independent neurophysiologists blinded to the patient's history. The median values of baseline pupil size, pupillary constriction, constriction velocity, and latency were collected for both eyes. To assess sensitivity and specificity, we calculated areas under the receiver-operating characteristic curve., Results: The degree of encephalopathy assessed by EEG was categorized as mild (42%), moderate (37%), severe (10%) or suppression-burst/suppression (12%); a total of 47/60 EEG recordings were classified as "reactive." There was a significant difference in pupillary size, constriction rate, and constriction velocity, but not latency, among the different EEG categories of encephalopathy. Similarly, reactive EEG tracings were associated with greater pupil size, pupillary constriction rate, and constriction velocity compared with nonreactive recordings; there were no significant differences in latency. Pupillary constriction rate values had an area under the curve of 0.83 to predict the presence of severe encephalopathy or suppression-burst/suppression, with a pupillary constriction rate of < 20% having a sensitivity of 85% and a specificity of 79%., Conclusions: Automated pupillometry can contribute to the assessment of cerebral dysfunction in critically ill patients., Competing Interests: M.O. received lecture fees from Neuroptics. The remaining authors have no conflicts of interest to disclose., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Alteration of the mechanisms of cerebral blood flow (CBF) regulation might contribute to the pathophysiology of sepsis-associated encephalopathy (SAE). However, previous clinical studies on dynamic cerebral autoregulation (dCA) in sepsis had several cofounders. Furthermore, little is known on the potential impairment of neurovascular coupling (NVC) in sepsis. The aim of our study was to determine the presence and time course of dCA and NVC alterations in a clinically relevant animal model and their potential impact on the development of SAE., Methods: Thirty-six anesthetized, mechanically ventilated female sheep were randomized to sham procedures (sham, n = 15), sepsis (n = 14), or septic shock (n = 7). Blood pressure, CBF, and electrocorticography were continuously recorded. Pearson's correlation coefficient Lxa and transfer function analysis were used to estimate dCA. NVC was assessed by the analysis of CBF variations induced by cortical gamma activity (Eγ) peaks and by the magnitude-squared coherence (MSC) between the spontaneous fluctuations of CBF and Eγ. Cortical function was estimated by the alpha-delta ratio. Wilcoxon signed rank and rank sum tests, Friedman tests, and RMANOVA test were used as appropriate., Results: Sepsis and sham animals did not differ neither in dCA nor in NVC parameters. A significant impairment of dCA occurred only after septic shock (Lxa, p = 0.03, TFA gain p = 0.03, phase p = 0.01). Similarly, NVC was altered during septic shock, as indicated by a lower MSC in the frequency band 0.03-0.06 Hz (p < 0.001). dCA and NVC impairments were associated with cortical dysfunction (reduction in the alpha-delta ratio (p = 0.03))., Conclusions: A progressive loss of dCA and NVC occurs during septic shock and is associated with cortical dysfunction. These findings indicate that the alteration of mechanisms controlling cortical perfusion plays a late role in the pathophysiology of SAE and suggest that alterations of CBF regulation mechanisms in less severe phases of sepsis reported in clinical studies might be due to patients' comorbidities or other confounders. Furthermore, a mean arterial pressure targeting therapy aiming to optimize dCA might not be sufficient to prevent neuronal dysfunction in sepsis since it would not improve NVC.

Normal rats are extremely tolerant to heterologous blood transfusion; however, after subcutaneous injection of noradrenaline, they lose this tolerance and respond with severe thrombohemorrhagic reactions both at the site of injection and in internal organs, particularly the kidney.In histological structure, the topical and general manifestations of this thrombohemorrhagic response are virtually identical with those of the local and general Sanarelli-Shwartzman phenomenon, respectively.Among the blood specimens tested, those of the dog, cat, rabbit, guinea pig, chicken and man were most effective in inducing this type of noradrenaline hypersensitivity. The blood of the duck and hamster as well as homologous rat blood proved to be virtually or completely inefficacious.The possible theoretical and clinical implications of a noradrenaline test for potential blood-borne thrombohemorrhagic factors are briefly discussed.